Potentiation of antibacterial activity of the MB - 1 siderophore - monobactam conjugate using 1 an efflux pump inhibitor

19 Preliminary enthusiasm over the encouraging spectrum and in vitro activity of siderophore conjugates 20 such as MB-1 has recently been tempered by unexpected variability in in vivo efficacy. The need for 21 these conjugates to compete for iron with endogenously-produced siderophores has exposed a 22 significant liability for this novel antibacterial strategy. Here, we have exploited dependence on efflux 23 for siderophore secretion in Pseudomonas aeruginosa, and provide evidence that efflux inhibition could 24 circumvent this in vivo-relevant resistance liability. 25 on S etem er 2, 2017 by gest httpaac.asm .rg/ D ow nladed fom